Substance abuse among American Indians (AI) is a critical health disparity and accounts for many life- threatening and deadly problems such as accidents, chronic liver disease, cirrhosis, homicide, and suicide. The high rate of substance abuse found among AI adolescents is believed to be associated with a variety of environmental and historical factors. These include poverty, historical trauma, bi-cultural stress, and changing tribal and family roles. There are few evaluated programs addressing early adolescent AI substance abuse. Tribal communities must be actively engaged in program development and implementation to ensure cultural relevance and sustainability of prevention programs. This project proposes to evaluate an after-school substance abuse prevention intervention, the Intertribal Talking Circle (ITC), targeting 6th grade AI youth in three AI communities: Ojibwe/Chippewa in Minnesota, Choctaw in Oklahoma, and Lumbee in North Carolina. A community-based participatory research approach will be used to culturally and technologically adapt the ITC. A two-condition controlled study will evaluate the efficacy of the ITC to increase AI youth Native self- reliance while decreasing AI youth substance use involvement. An adult training program second level intervention study is also proposed to train tribal personnel from the three regional tribes on how to implement the Intertribal Talking Circle intervention as a tribl program beyond the study period. Effectiveness will be determined by a small partial cross-over randomized trial comparing ITC intervention to a Wait-List Control (WLC) condition. Process evaluations will focus on the future adoption and implementation of the ITC, and recommendations for sustainable adaptations. The project will also build AI capacity to address health disparities, as experienced Native investigators will mentor three Junior Native Investigators.